Role of the serine-rich surface glycoprotein GspB of Streptococcus gordonii in the pathogenesis of infective endocarditis

Xiong, Yan Q.; Bensing, Barbara A.; Bayer, Arnold S.; Chambers, Henry F.; Sullam, Paul M.

doi:10.1016/j.micpath.2008.06.004

Cited by 98 publications

(125 citation statements)

References 35 publications

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“…For example, several surface proteins of Gram-positive bacteria, mediating platelet aggregation, have been demonstrated to be important for virulence in animal models of IE [22][23][24][25]. However, platelet activation by Grampositive pathogens most often requires specific host IgG, perhaps indicating that platelet activation should be regarded as a host immune response.…”

Section: Discussionmentioning

confidence: 99%

Clinical isolates of Enterococcus faecalis aggregate human platelets

Rasmussen

Johansson

Söbirk

et al. 2010

Microbes and Infection

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Many endocarditis pathogens activate human platelets and this has been proposed to contribute to virulence. Here we report for the first time that many clinical isolates of Enterococcus faecalis, a common pathogen in infective endocarditis, aggregate human platelets. 84 isolates from human blood and urine were screened for their ability to aggregate platelets from four different donors. Platelet aggregation occurred for between 11 and 65 % of isolates depending on the donor. In one donor, a significantly larger proportion of isolates from blood than from urine caused platelet aggregation. Median time to aggregation was 11 minutes and had a tendency to be shorter for blood isolates as compared to urine isolates.Immunoglobulin G (IgG) was shown to be essential in mediating activation and aggregation. Platelet aggregation could be abolished by an IgG-specific proteinase (IdeS), by an antibody blocking FcRIIa on platelets, or by preabsorption of plasma with an E. faecalis isolate. Fibrinogen binding to bacteria or platelets does not contribute to platelet activation or aggregation under our experimental conditions. These results indicate that platelet activation and aggregation by E. faecalis is dependent on both host and bacterial factors and that it may be involved in the pathogenesis of invasive disease with this organism.

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Section: Discussionmentioning

confidence: 99%

Clinical isolates of Enterococcus faecalis aggregate human platelets

Rasmussen

Johansson

Söbirk

et al. 2010

Microbes and Infection

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“…Importantly, inactivation of either hsa or gspB results in a reduction in Strep. gordoniimediated infective endocarditis in a rat model (Takahashi et al, 2006;Xiong et al, 2008). The interaction of GspB with host components has been studied extensively; GspB not only binds to human platelets but also interacts with a variety of salivary components such as the low-molecular- mass salivary mucin MG2 and salivary agglutinin (gp340) (Takamatsu et al, 2006).…”

Section: Serine-rich Glycoproteins Play Important Roles In Bacterial mentioning

confidence: 99%

Glycosylation and biogenesis of a family of serine-rich bacterial adhesins

2009

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Glycosylation of bacterial proteins is an important process for bacterial physiology and pathophysiology. Both O-and N-linked glycan moieties have been identified in bacterial glycoproteins. The N-linked glycosylation pathways are well established in Gram-negative bacteria. However, the O-linked glycosylation pathways are not well defined due to the complex nature of known O-linked glycoproteins in bacteria. In this review, we examine a new family of serine-rich O-linked glycoproteins which are represented by fimbriae-associated adhesin Fap1 of Streptococcus parasanguinis and human platelet-binding protein GspB of Streptococcus gordonii. This family of glycoproteins is conserved in streptococcal and staphylococcal species. A gene cluster coding for glycosyltransferases and accessory Sec proteins has been implicated in the protein glycosylation. A two-step glycosylation model is proposed. Two glycosyltransferases interact with each other and catalyse the first step of the protein glycosylation in the cytoplasm; the cross-talk between glycosylation-associated proteins and accessory Sec components mediates the second step of the protein glycosylation, an emerging mechanism for bacterial Olinked protein glycosylation. Dissecting the molecular mechanism of this conserved biosynthetic pathway offers opportunities to develop new therapeutic strategies targeting this previously unrecognized pathway, as serine-rich glycoproteins have been shown to play a role in bacterial pathogenesis.

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“…This surface component mediates host adherence via a binding region that promotes a high affinity interaction to a narrow range of sialylated carbohydrates (10). Studies using recombinant GspB and whole bacteria have shown that the binding of GspB to the sialylated glycans of GPIb␣ is the primary adhesive interaction to host platelets (7,9,11) and that expression of GspB enhances virulence (12).…”

mentioning

confidence: 99%

Structural Basis for Sialoglycan Binding by the Streptococcus sanguinis SrpA Adhesin

Bensing

Loukachevitch

McCulloch

et al. 2016

Journal of Biological Chemistry

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Streptococcus sanguinis is a leading cause of infective endocarditis, a life-threatening infection of the cardiovascular system. An important interaction in the pathogenesis of infective endocarditis is attachment of the organisms to host platelets. S. sanguinis expresses a serine-rich repeat adhesin, SrpA, similar in sequence to platelet-binding adhesins associated with increased virulence in this disease. In this study, we determined the first crystal structure of the putative binding region of SrpA (SrpA BR ) both unliganded and in complex with a synthetic disaccharide ligand at 1.8 and 2.0 Å resolution, respectively. We identified a conserved Thr-Arg motif that orients the sialic acid moiety and is required for binding to platelet monolayers. Furthermore, we propose that sequence insertions in closely related family members contribute to the modulation of structural and functional properties, including the quaternary structure, the tertiary structure, and the ligand-binding site.

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Role of the serine-rich surface glycoprotein GspB of Streptococcus gordonii in the pathogenesis of infective endocarditis

Cited by 98 publications

References 35 publications

Clinical isolates of Enterococcus faecalis aggregate human platelets

Clinical isolates of Enterococcus faecalis aggregate human platelets

Glycosylation and biogenesis of a family of serine-rich bacterial adhesins

Structural Basis for Sialoglycan Binding by the Streptococcus sanguinis SrpA Adhesin

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